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Tung Tran, MD
Director, Durham VA Epilepsy Center of Excellence (ECoE)
Assistant Professor of Neurology, Duke University
ECoE Patient Education Audio Conference
April 3, 2014
Antiepileptic Drugs (AEDs) & Seizures Definitions
Why start AED treatment?
How AEDs work
Side effects
Picking the right medication
Specific AEDs Commonly used AEDs
Seizures are abnormal (surge) patterns of brain electrical activity which disrupt normal function
There are different types of epileptic seizures May arise from part of the brain
May arise from the whole brain
Behavior often has certain characteristic qualities
EEG (electroencephalography) measures brain electrical activity, noninvasively
Other non-epileptic behaviors often look like epileptic seizures
Recurring seizures Usually requires 2 unprovoked seizures
Implies continued risk of further seizures Usually leads to medication treatment
Prevent negative effects of seizures For example, injuries due to loss of awareness
May reduce restrictions of seizure precautions For example, driving
There are consequences to being on a medication Cost of effort, time and money
All medications have potential for side effects
Stigma associated with taking medications for seizures
Prevents all future seizures Thus, no further consequence from seizures
One time treatment Minimal effort and time requirement
Cheap Minimal cost
No side effect
“No Seizures, No Side Effects”
When having clear recurrent epileptic seizures May be the result of other tests, such as
EEG
Imaging (e.g., MRI)
History
When concerned about future seizures Estimates for next seizure after one unprovoked seizure:
25% within 6 months
30% within 1 year
40% within 2 years
50% within 5 years
Electrical activity in the brain requires certain chemicals and structures for it to work
Seizures can be thought of as hyperactive brain activity
Therefore, medications which reduce the chance of having seizures tend to change the amount of chemicals or structures that direct brain activity They may decrease or increase concentrations
Different AEDs work on different groups of chemicals Often affect multiple chemicals
May be delivered to the brain through different paths
All these factors determine how AEDs work and their side effects
There is no best medication for all of epilepsy
If seizure medications try to reduce the abnormal excessive brain activities of seizures, then those functions which depend on brain firing may be affected Thinking
Wakefulness
Emotions
Other side effects may be due to how the medication is processed Interactions with other medications
Monitoring of liver function (metabolism)
The amount of medication in the body can often be measured via blood draws
“Recommended” drug levels are based on studies across patients Effective & toxic levels vary across individuals
We treat the PATIENT and NOT just the Lab Values Dosage depends on seizure control and side effects
May be useful to know if levels are very low or if someone is/will be pregnant
In theory, there should not be a significant difference
However, recall that Effective & toxic levels vary across individuals
In general, the more economical generic medication should be tried and failure documented before Brand options are requested
Medications can vary by Frequency required (e.g., once a day)
Form of medication (e.g., tablets, liquid, IV, etc.)
Some formulations of a medication may be non-formulary (have limitations of use within the VHA)
Which medication to start? Again, there is no universal best AED May be influenced by type of seizure
“Focal” versus “primary generalized”
Convenience For example, method or frequency of administration
Cost and availability Possible side effects
For example, mental status, weight, job, other meds, etc.
Experience and comfort
How to start that medication
What if a medication fails?
Which medication to start?
How to start that medication “Start low and go slow”
People are different
Increase single medication until seizures stop or medication not tolerated
What if a medication fails?
Which medication to start?
How to start that medication
What if a medication fails? Most common cause of breakthrough seizures is not taking
the medication Let your practitioner know if you do not tolerate a medication or
often forget to take them
Minimize number of medications taken at same time However, there is often an overlap period for transition
Sometimes, a combination of AEDs is helpful Most people (>60%) can have their seizures controlled with
AEDs, but for those who fail three or more AEDs, surgery should be considered
Phenobarbital1912
Phenytoin (Dilantin)1938
Valproate (Depakote)1978
Carbamazepine(Tegretol)1974
Oxcarbazepine (Trileptal)1999
Ethosuximide (Zarontin)1960
Benzodiazapines
Levetiracetam (Keppra) 2000
Lamotrigine (Lamictal) 1995
Lacosamide (Vimpat) 2008
Pregabalin (Lyrica) 2005
Gabapentin (Neurontin) 1994
Topiramate (Topamax) 1996
Zonisamide (Zonegran) 2000
1st Generation
2nd Generation
3rd Generation
Clobazam (Onfi) 2011
Ezogabine (Potiga) 2011
Perampanel (Fycompa) 2013
Felbamate (Felbatol) 1993
Rufinamide (Banzel) 2008
Vigabatrin (Sabril) 2009
Tiagabine (Gabitril) 1997
Primidone (Mysoline) 1954
Eslicarbazepine
Breviracetam
Seizure-type indication
Metabolism (how it is processed)
Some possible side effects
Comments
Broad spectrum Avoid in absence & myoclonic seizures
Enzyme inducer (liver metabolism) & long half-life
Somnolence/cognition & behavioral (dose)
Long term effects on bone health
Wean down slowly
Used less frequently now than previously
Usually used with partial seizures
Levels nonlinear (hard to control) & enzyme inducer
Toxic: Dizziness, coordination, sedation/cognition
Long term: Osteoporosis, gingival hyperplasia, cerebellar syndrome
IV form available, generic, common
Broad spectrum (e.g., absence, myoclonic)
Inhibits metabolism
Somnolence/cognition (ammonia), weight gain, hair loss, tremor
Liver & pancreas toxicities, low platelets, teratogen
IV form available, generic, common
Partial seizures
Enzyme inducer
Coordination, diplopia, somnolence, nausea
Rash (HLA-B Asians), blood reactions, low sodium, liver toxicity, osteoporosis
Generic, common
Partial seizures Pro-drug of carbamazepine, often better tolerated
Not self-inducing, but still involved liver metabolism
Dizziness, diplopia, rash, low sodium
Recently was non-formulary
Partial (and generalized) seizures
Minimal drug interactions
Mood disturbance (irritability), somnolence
Relatively easy to use
Partial and generalized seizures Except for severe myoclonic
May be affected by enzyme-inducers/inhibitors
Rash, & some dizziness, mild tremor, less sedation
Slow titration up; increase in pregnancy
Partial (& generalized) seizures
Minimal drug interactions
Dizziness, gait difficulties, nausea
Watch if history of EKG abnormalities (PR increase)
Non-formulary, still brand-only
Partial seizures
Minimal drug interactions
Peripheral edema (weight gain), somnolence, dizziness
Used often for chronic pain & neuropathy
Partial seizures
Minimal drug interactions
Edema/weight gain, dizziness/somnolence
Similar to gabapentin, but non-formulary
Partial and generalized seizures
Some hepatic induction
Cognition/somnolence, weight loss
Kidney stones, glaucoma, metabolic acidosis
Partial (& generalized) seizures
Cognition, weight loss, kidney stones, rash
Recently was non-formulary
Because of relative lack of drug interactions, lamotrigine and levetiracetam are commonly used in elderly patients
For women of child-bearing age, valproate is typically avoided. Lamotrigine, levetiracetram and zonisamide are commonly used.
Antiepileptic Drugs (AEDs) & Seizures Definitions
Why start AED treatment?
How AEDs work
Side effects
Picking the right medication
Specific AEDs Commonly used AEDs
Benefits versus Risks
Work with your practitioner Let them know how things are going
Seizure frequency and side effects
Please let them know if you cannot take a medication
For more information: http://www.epilepsy.va.gov/
Thank you
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